The Impact of T Cell Intrinsic Antigen Adaptation on Peripheral Immune Tolerance

Overlapping roles have been ascribed for T cell anergy, clonal deletion, and regulation in the maintenance of peripheral immunological tolerance. A measurement of the individual and additive impacts of each of these processes on systemic tolerance is often lacking. In this report we have used adoptive transfer strategies to tease out the unique contribution of T cell intrinsic receptor calibration (adaptation) in the maintenance of tolerance to a systemic self-antigen. Adoptively transferred naïve T cells stably calibrated their responsiveness to a persistent self-antigen in both lymphopenic and T cell–replete hosts. In the former, this state was not accompanied by deletion or suppression, allowing us to examine the unique contribution of adaptation to systemic tolerance. Surprisingly, adapting T cells could chronically help antigen-expressing B cells, leading to polyclonal hypergammaglobulinemia and pathology, in the form of mild arthritis. The helper activity mediated by CD40L and cytokines was evident even if the B cells were introduced after extended adaptation of the T cells. In contrast, in the T cell–replete host, neither arthritis nor autoantibodies were induced. The containment of systemic pathology required host T cell–mediated extrinsic regulatory mechanisms to synergize with the cell intrinsic adaptation process. These extrinsic mechanisms prevented the effector differentiation of the autoreactive T cells and reduced their precursor frequency, in vivo

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing life-long therapy to a global population of over 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

Haym Salomon collection undated, 1777-1982

Contains a number of original manuscripts of Haym Salomon including his marriage contract with Rachel Franks (1777), a bank note signed by Francis Hopkinson, Treasurer of Loans (1780), 2 bank drafts in French (1784), a letter book containing both personal and business correspondence (1781-1783), a letter from Abraham I. Abrahams (1783), documents relating to estate of Barnet Levy (1784) and several sales lists (1784). Also contains a family record kept by his son, Haym Moses Salomon; a set of Bibles sold to H.M. Salomon by Ephraim Hart, and given to his son David Salomon, which contains family records and lists of children of Haym Salomon and Haym M. Salomon; several prayer books belonging to the Salomon family; several letters of Ezekiel Salomon (1819) and a petition of Rachel Helborne, widow of Haym Salomon, to Orphan's Court, Philadelphia (1787), requesting appointment of guardians for childrenCollection also contains correspondence, printed material and data relating to Haym Salomon, particularly to his financial role in the Revolutionary War and the validity of his descendants' claims for reimbursement, and to the controversy over the erection of a Haym Salomon monument in Madison Square in New York City, including a report and related material by Samuel Oppenheim (1926) and a report and letters of Ruth L. Benjamin (1927) to a sub-committee composed of Max J. Kohler, Leon Huhner and Albert M. Friedenberg and reports by the overall committee organized by Judge Grossman (1925-1927) relating to Salomon's role in the Revolution; a report of a sub-committee of the New York City ... Commission (1925); material ... pertaining to the work of the Haym Salomon Monument Committee of the Federation of Polish Jews in America; correspondence of Kohler and a typed bibliography with transcriptions of various documents prepared by Laura L. Nichols of the Library of Congress1 reel of microfilm, not clear which part of the collection is filmedfar031